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Byline: Fei-Fei. Chen, Feng. Jiang, Wen-Wen. Zhang, Ya-Jun. Liu, Zi-Fang. He, Zheng-Gao. Xie To evaluate a novel technique for six-point scleral fixation of a three-looped haptics posterior chamber intraocular lens [...]

Byline: Wen-Wen. Zhang, Fei-Fei. Chen, Ya-Jun. Liu, Feng. Jiang, Zheng-Gao. Xie When primary angle-closure glaucoma occurs during an acute attack, routine phacoemulsification is challenging because of the high intra-ocular pressure [...]

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure–activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4containing imidazo[1,2-a]pyridine. Importantly, I-c4effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4could mitigate severe myocardial damage against H2O2or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4was associated with reduction of inflammatory cytokines. Taken together, I-c4may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS.

IMPORTANCE: Artificial intelligence (AI) chatbots pose the opportunity to draft template responses to patient questions. However, the ability of chatbots to generate responses based on domain-specific knowledge of cancer remains to be tested. OBJECTIVE: To evaluate the competency of AI chatbots (GPT-3.5 [chatbot 1], GPT-4 [chatbot 2], and Claude AI [chatbot 3]) to generate high-quality, empathetic, and readable responses to patient questions about cancer. DESIGN, SETTING, AND PARTICIPANTS: This equivalence study compared the AI chatbot responses and responses by 6 verified oncologists to 200 patient questions about cancer from a public online forum. Data were collected on May 31, 2023. EXPOSURES: Random sample of 200 patient questions related to cancer from a public online forum (Reddit r/AskDocs) spanning from January 1, 2018, to May 31, 2023, was posed to 3 AI chatbots. MAIN OUTCOMES AND MEASURES: The primary outcomes were pilot ratings of the quality, empathy, and readability on a Likert scale from 1 (very poor) to 5 (very good). Two teams of attending oncology specialists evaluated each response based on pilot measures of quality, empathy, and readability in triplicate. The secondary outcome was readability assessed using Flesch-Kincaid Grade Level. RESULTS: Responses to 200 questions generated by chatbot 3, the best-performing AI chatbot, were rated consistently higher in overall measures of quality (mean, 3.56 [95% CI, 3.48-3.63] vs 3.00 [95% CI, 2.91-3.09]; P < .001), empathy (mean, 3.62 [95% CI, 3.53-3.70] vs 2.43 [95% CI, 2.32-2.53]; P < .001), and readability (mean, 3.79 [95% CI, 3.72-3.87] vs 3.07 [95% CI, 3.00-3.15]; P < .001) compared with physician responses. The mean Flesch-Kincaid Grade Level of physician responses (mean, 10.11 [95% CI, 9.21-11.03]) was not significantly different from chatbot 3 responses (mean, 10.31 [95% CI, 9.89-10.72]; P > .99) but was lower than those from chatbot 1 (mean, 12.33 [95% CI, 11.84-12.83]; P < .001) and chatbot 2 (mean, 11.32 [95% CI, 11.05-11.79]; P = .01). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that chatbots can generate quality, empathetic, and readable responses to patient questions comparable to physician responses sourced from an online forum. Further research is required to assess the scope, process integration, and patient and physician outcomes of chatbot-facilitated interactions.

The generation of waste printed circuit boards (WPCBs) is increasing due to the global consumption of electronic devices. In this study, a novel approach has been proposed by employing pyrolysis oil derived from the pyrolysis of non-metallic particles (NMPs) as self-generated collector for WPCBs flotation, thereby improves the flotation effect of WPCBs, which not only circumventing the consumption of non-regenerative collectors but also offering a viable means for the clean utilization of non-metallic components (NMCs). The surface morphology and phase composition of WPCBs and NMPs were analyzed respectively. The SEM and XRD results indicate that the dissociation degree of NMPs is limited, thereby exacerbating the challenges associated with flotation of WPCBs. Additionally, FTIR analysis was conducted to investigate the adsorption mechanism between pyrolysis oil and NMPs. The results show that both NMPs and pyrolysis oil contain -CH3, CC diffraction peaks, which is conducive to the adsorption of pyrolysis oil. The floatability of NMPs before and after conditioned by pyrolysis oil, as well as the mechanism of particle-bubble interaction, were investigated through contact angle and wrap angle measurements. The results demonstrate a substantial increase of over 45° in the contact angle of NMPs. Additionally, the results show that the wrap angles of NMPs conditioned by pyrolysis oil also significantly increase. Flotation tests with pyrolysis oil were conducted on WPCBs and NMPs to validate the effectiveness of pyrolysis oil on flotation. The flotation results of WPCBs show that when 8 kg/t pyrolysis oil is added, the Cu grade for concentrate of 1–0.5, 0.5–0.25, 0.25–0.125, 0.125–0.074, −0.074 mm increases by 4.24 %, 10.26 %, 17.86 %, 17.20 %, and 22.21 %, respectively. This study presents a viable approach to address the challenges of achieving higher separation accuracy for WPCBs and optimizing resource utilization of NMPs.

The El Niño–Southern Oscillation (ENSO) provides most of the global seasonal climate forecast skill1–3, yet, quantifying the sources of skilful predictions is a long-standing challenge4–7. Different sources of predictability affect ENSO evolution, leading to distinct global effects. Artificial intelligence forecasts offer promising advancements but linking their skill to specific physical processes is not yet possible8–10, limiting our understanding of the dynamics underpinning the advancements. Here we show that an extended nonlinear recharge oscillator (XRO) model shows skilful ENSO forecasts at lead times up to 16–18 months, better than global climate models and comparable to the most skilful artificial intelligence forecasts. The XRO parsimoniously incorporates the core ENSO dynamics and ENSO’s seasonally modulated interactions with other modes of variability in the global oceans. The intrinsic enhancement of ENSO’s long-range forecast skill is traceable to the initial conditions of other climate modes by means of their memory and interactions with ENSO and is quantifiable in terms of these modes’ contributions to ENSO amplitude. Reforecasts using the XRO trained on climate model output show that reduced biases in both model ENSO dynamics and in climate mode interactions can lead to more skilful ENSO forecasts. The XRO framework’s holistic treatment of ENSO’s global multi-timescale interactions highlights promising targets for improving ENSO simulations and forecasts.

Beyond traditional paper, multifunctional nanopaper has received much attention in recent years. Currently, many nanomaterials have been successfully used as building units of nanopaper. However, it remains a great challenge to prepare flexible and freestanding metal–organic framework (MOF) nanopaper owing to the low aspect ratio and brittleness of MOF nanocrystals. Herein, this work develops a flexible and free-standing MOF nanopaper with MOF nanowires as building units. The manganese-based MOF (Mn-MOF) nanowires with lengths up to 100 μm are synthesized by a facile solvothermal method. Through a paper-making technique, the Mn-MOF nanowires interweave with each other to form a three-dimensional architecture, thus creating a flexible and free-standing Mn-MOF nanowire paper. Furthermore, the surface properties can be engineered to obtain high hydrophobicity by modifying polydimethylsiloxane (PDMS) on the surfaces of the Mn-MOF nanowire paper. The water contact angle reaches 130°. As a proof of concept, this work presents two potential applications of the Mn-MOF/PDMS nanowire paper: (i) The as-prepared Mn-MOF/PDMS nanowire paper is compatible with a commercial printer. The as-printed colorful patterns are of high quality, and (ii) benefiting from the highly hydrophobic surfaces, the Mn-MOF/PDMS nanowire paper is able to efficiently separate oil from water.

Perovskite solar cells (PSCs) have shown great potential for reducing costs and improving power conversion efficiency (PCE). One effective method to achieve the latter is to use an all-inorganic charge transport layer (ICTL). However, traditional methods for crystallizing inorganic layers often result in the formation of a powder instead of a continuous film. To address this issue, we designed a dual-layer inorganic electron transport layer (IETL). This dual-layer structure consists of a layer of SnO2nanocrystals (SnO2NCs) deposited via a solution process and a dense SnO2layer deposited through atomic layer deposition (ALD SnO2) to fill the cracks and gaps between the SnO2NCs. PSCs having these dual-layer SnO2ETLs achieved a high efficiency of 23.0%. This efficiency surpasses the recorded performance of ICTLs deposited on the perovskite. Furthermore, the PCE is comparable to that achieved with a C60 ETL. Moreover, the high-density structure of the ALD SnO2layer inhibits the vertical migration of ions, resulting in improved thermal stability. After continuous heating at 85 °C in 10% humidity for 1000 h, the PCE of the dual-layer SnO2structure decreased by 18%, whereas that of the C60/BCP structure decreased by 36%. The integration of dual-layer SnO2into PSCs represents a significant advancement in achieving high-performance, commercially viable inverted monolithic PSCs or tandem solar cells.

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.

Detecting cyanobacteria in environments is an important concern due to their crucial roles in ecosystems, and they can form blooms with the potential to harm humans and nonhuman entities. However, the most widely used methods for high-throughput detection of environmental cyanobacteria, such as 16S rRNA sequencing, typically provide above-species-level resolution, thereby disregarding intraspecific variation. To address this, we developed a novel DNA microarray tool, termed the CyanoStrainChip, that enables strain-level comprehensive profiling of environmental cyanobacteria. The CyanoStrainChip was designed to target 1277 strains; nearly all major groups of cyanobacteria are included by implementing 43,666 genome-wide, strain-specific probes. It demonstrated strong specificity by in vitromock community experiments. The high correlation (Pearson’s R> 0.97) between probe fluorescence intensities and the corresponding DNA amounts (ranging from 1–100 ng) indicated excellent quantitative capability. Consistent cyanobacterial profiles of field samples were observed by both the CyanoStrainChip and next-generation sequencing methods. Furthermore, CyanoStrainChip analysis of surface water samples in Lake Chaohu uncovered a high intraspecific variation of abundance change within the genus Microcystisbetween different severity levels of cyanobacterial blooms, highlighting two toxic Microcystisstrains that are of critical concern for Lake Chaohu harmful blooms suppression. Overall, these results suggest a potential for CyanoStrainChip as a valuable tool for cyanobacterial ecological research and harmful bloom monitoring to supplement existing techniques.

AbstractBackgroundThe purpose of this systematic review and meta-analysis was to evaluate the common clinical adverse events associated with sodium/glucose cotransporter-2 inhibitor (SGLT2i) use compared to placebo in patients with chronic kidney disease (CKD) with or without type 2 diabetes.MethodsTwelve articles were chosen viaa systematic search of the PubMed, Embase, and Cochrane Library databases. We screened for randomised placebo-controlled trials. The main clinical adverse events included diabetes ketoacidosis (DKA), amputation, and volume depletion. We performed heterogeneity testing and assessment of publication bias.ResultsIn all, 65 600 patients were included in the analysis. Compared to placebo, SGLT2i may increase the risk of DKA and volume depletion in patients with CKD with or without type 2 diabetes. For DKA, compared with placebo, the combined effect of SGLT2i was OR 2.03 (95% CI: 1.28 to 3.23 I2: 2.3%, P: 0.420). For volume depletion, compared with placebo, the combined effect of SGLT2i was OR 1.24 (95% CI: 1.13 to 1.37 I2: 0.0%, P: 0.484). For the risk of amputation, despite low heterogeneity for amputation, the forest plot indicated no statistical significance, and thus it cannot be concluded that SGLT2i increases the risk of amputation. Compared with placebo, the combined effect of SGLT2i was OR 1.10 (95% CI: 0.94 to 1.29 I2: 0.0%, P: 0.642).ConclusionThe use of SGLT2i may increase the risk of DKA and volume depletion in patients with chronic renal insufficiency with or without type 2 diabetes.

Background: In this ever-expanding treatment landscape, there is a lack of consolidated health-related quality of life (HRQOL) outcomes and utility reports in relapsed or refractory (R/R) large B cell lymphoma (LBCL) to inform health care policy and decision-maker assessments for both old and new products. These assessments can have a direct effect on what treatment options are available to patients and physicians. Objective: A systematic literature review (SLR) was performed to understand the HRQOL evidence for treatments in R/R LBCL and identify associated health utility values. Methods: The SLR searched and screened literature published from 1 January 2003 to 2 May 2022. Studies were screened based on Population, Intervention, Comparator, Outcome, Study design criteria established a priori and were assessed by two independent reviewers; quality assessments of the evidence were performed in accordance with health technology assessment recommendations from the National Institute for Health and Care Excellence. Several types of therapies were included, such as chimeric antigen receptor (CAR) T cell products (lisocabtagene maraleucel, axicabtagene ciloleucel, tisagenlecleucel), novel therapies (selinexor, nivolumab, polatuzumab vedotin, and bendamustine), salvage therapies, and rituximab. Results: The review identified 33 unique studies reporting HRQOL, including 15 economic studies that reported health state utility values, 9 clinical trials, 7 health technology assessment reports, and 1 each of a vignette-based study and a point-in-time survey. Improvements in general and/or lymphoma-specific HRQOL measures were observed with CAR T cell therapy in both the second-line and third-line or later settings. On-treatment utility values for CAR T cell therapies ranged from 0.50 to 0.74. Values for remission/progression-free survival (0.70–0.90) and for disease progression (0.39–0.59) were similar across studies. For novel therapies, utility values were 0.83 for progression-free survival and ranged from 0.39 to 0.71 for disease progression. On-treatment utility values for salvage chemotherapy ranged from 0.63 to 0.67. Conclusions: Overall, the evidence synthesized in this SLR provides a comprehensive understanding of the HRQOL evidence in R/R LBCL. This article identified several sources for utility values in the published literature showing variation in the HRQOL outcomes for patients across a variety of therapeutics. Treatment of R/R LBCL with CAR T cell therapies was associated with improvement in health utility values. Mixed results were found for novel therapies and salvage therapies. More data are needed as new therapies are used in this patient population to inform treatment decision-making.

The global oceans absorb most of the surplus heat from anthropogenic warming, but it is unclear how this heat accumulation will affect the Earth’s climate under climate mitigation scenarios. Here we show that this stored heat will be released at a much slower rate than its accumulation, resulting in a robust pattern of surface ocean warming and consequent regional precipitation. The surface ocean warming is pronounced over subpolar to polar regions and the equatorial eastern Pacific where oceans are weakly stratified to allow vigorous heat release from the deep ocean to the surface layer. We also demonstrate that this ocean warming pattern largely explains changes in the precipitation pattern, including the southward shift of the Intertropical Convergence Zone and more moistening in high latitudes. This study suggests that deep ocean warming may hinder climate recovery in some regions, even if carbon neutrality or net negative emissions are successfully achieved.

Peripheral blood involvement by MF/SS has significant implications for prognosis and treatment. Flow cytometry is commonly used to assess MF/SS by analyzing the ratio of CD26- and/or CD7-CD4 + T cells and assessment of immunophenotypic abnormalities. However, distinguishing normal from abnormal cells is not always easy. In this study, we aimed to establish quantitative thresholds to better distinguish normal CD4 + T cells from neoplastic CD4 + T cells. A retrospective analysis of flow cytometry data was performed on 30 MF/SS patients with a detectable abnormal T cell population (positive), 63 patients with suspected or confirmed cutaneous involvement without a detectable abnormal T cell population (negative), and 60 healthy controls (control). CD3 and CD4 median fluorescence intensity (MFI) was normalized to internal control subsets. Among the positive cases, 50% had CD3 expression outside ± 2 SD from the mean of the negative and control group in the CD4 + CD26- subset. The corresponding specificity of this threshold was 94%. The ± 2 SD threshold showed a sensitivity of 57% and a specificity of 94% for the CD3 intensity among the CD7-negative subset. For CD4 intensity, the ± 2 SD threshold had a sensitivity of 33.3% and specificity of 95% for the CD26-negative subset and a sensitivity of 37% and specificity of 95% for the CD7-negative subset. In our study, although changes in CD3 and CD4 intensity greater than ± 2 SD were specific for MF/SS, more subtle differences in the intensity of CD3 and CD4 should not be used as the sole abnormality to make a diagnosis of circulating MF/SS.

Endometrial cancer (EC) is a common malignancy among women worldwide, and its recurrence makes it a common cause of cancer-related death. Surgery and external radiation, chemotherapy, or a combination of strategies are the cornerstone of therapy for EC patients. However, adjuvant treatment strategies face certain drawbacks, such as resistance to chemotherapeutic drugs; therefore, it is imperative to explore innovative therapeutic strategies to improve the prognosis of EC. With the development of pathology and pathophysiology, several biological targets associated with EC have been identified, including PI3K/Akt/mTOR, PARP, GSK-3β, STAT-3, and VEGF. In this review, we summarize the progress of small molecule targeted therapies in terms of both basic research and clinical trials and provide cases of small molecules combined with fluorescence properties in the clinical applications of integrated diagnosis and treatment. We hope that this review will facilitate the further understanding of the regulatory mechanism governing the dysregulation of oncogenic signaling in EC and provide insights into the possible future directions of targeted therapeutic regimens for EC treatment by developing new agents with fluorescence properties for the clinical applications of integrated diagnosis and treatment.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15(5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15significantly reduced Aβ accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15and the necessity of the CaMKIIα/Fos for FO-4-15was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15and mGluR1 was displayed by Ca2+flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15may hold promise as a potential treatment for Alzheimer’s disease.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers viaendoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (−559/−429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3’UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP viathe regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing’s anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing’s pharmacologically significant constituents supports the medicine’s anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Regulating charge transfer and reaction pathways are effective strategies for boosting photocatalytic CO2reduction. Herein, Co3O4/ZrO2mesoporous octahedrons are synthesized through facile pyrolysis of UIO-66@ZIF-67 core/shell octahedrons. The as-obtained Co3O4/ZrO2mesoporous octahedrons are assembled by highly dispersive and small-sized nanoparticles, with 13 nm average particle size and 5.8 nm pore width, leading to a high specific surface area of 43.11 m2g−1. Benefiting from active-site engineering, the charge-transfer kinetics and CO2adsorption are successfully enhanced. In addition, density functional theory calculations reveal that ZrO2tailors the reaction pathway of CO2reduction by promoting CO2activation to *CO2and intermediate formation (*COOH and *CO), as well as decreasing the energy barrier of the rate-limiting step (*CO→CO). Thus, the Co3O4/ZrO2mesoporous octahedrons afford a turnover frequency of 28.82 h−1, 16.95-fold larger than pure Co3O4.

The O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) is a critical post-translational modification that couples the external stimuli to intracellular signal transduction networks. However, the critical protein targets of O-GlcNAcylation in oxidative stress-induced apoptosis remain to be elucidated. Here, we show that treatment with H2O2inhibited O-GlcNAcylation, impaired cell viability, increased the cleaved caspase 3 and accelerated apoptosis of neuroblastoma N2a cells. The O-GlcNAc transferase (OGT) inhibitor OSMI-1 or the O-GlcNAcase (OGA) inhibitor Thiamet-G enhanced or inhibited H2O2-induced apoptosis, respectively. The total and phosphorylated protein levels, as well as the promoter activities of signal transducer and activator of transcription factor 3 (STAT3) and Forkhead box protein O 1 (FOXO1) were suppressed by OSMI-1. In contrast, overexpressing OGT or treating with Thiamet-G increased the total protein levels of STAT3 and FOXO1. Overexpression of STAT3 or FOXO1 abolished OSMI-1-induced apoptosis. Whereas the anti-apoptotic effect of OGT and Thiamet-G in H2O2-treated cells was abolished by either downregulating the expression or activity of endogenous STAT3 or FOXO1. These results suggest that STAT3 or FOXO1 are the potential targets of O-GlcNAcylation involved in the H2O2-induced apoptosis of N2a cells.

ABSTRACTHigh strength structural steels have recently achieved increasing application in civil and structural engineering worldwide. For instance, the sony center tower located in Berlin were constructed through steel truss made [...]

Toxoplasma gondiiinfection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondiiinduces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondiiinfection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii–infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1β and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii–infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii–infected cells reversed these effects. Collectively, these findings show that T. gondiiinduces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1–mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis.

Extreme low-temperature incidents have become more frequent and severe as climate change intensifies. In Huang-Huai-Hai wheat growing area of China, the late spring coldness occurring at the jointing-booting stage (the anther interval stage) has resulted in significant yield losses of winter wheat. This study attempts to develop an economical, feasible, and efficient cultivation technique for improving the low-temperature (LT) resistance of wheat by exploring the effects of twice-split phosphorus application (TSPA) on wheat antioxidant characteristics and carbon and nitrogen metabolism physiology under LT treatment at the anther interval stage using Yannong 19 as the experimental material. The treatments consisted of traditional phosphorus application and TSPA, followed by a –4°C LT treatment and natural temperature (NT) control at the anther interval stage. Our analyses showed that, compared with the traditional application, the TSPA increased the net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of leaves and reduced the intercellular carbon dioxide concentration (Ci). The activity of carbon and nitrogen metabolism enzymes in the young wheat spikes was also increased by the TSPA, which promoted the accumulation of soluble sugar (SS), sucrose (SUC), soluble protein (SP), and proline (Pro) in young wheat spike and reduced the toxicity of malondialdehyde (MDA). Due to the improved organic nutrition for reproductive development, the young wheat spikes exhibited enhanced LT resistance, which reduced the sterile spikelet number (SSN) per spike by 11.8% and increased the spikelet setting rate (SSR) and final yield by 6.0 and 8.4%, respectively, compared to the traditional application. The positive effects of split phosphorus application became more pronounced when the LT treatment was prolonged.

Hybrid organic–inorganic perovskites (HOIPs) have exhibited striking application potential in piezoelectric energy harvesting and sensing due to their high piezoelectricity, light weight, and solution processability. However, to date, the application of piezoelectric HOIPs in ultrasound detection has not yet been explored. Here, we report the synthesis of a pair of chiral two-dimensional piezoelectric HOIPs, R-(4-bromo-2-butylammonium)2PbBr4and S-(4-bromo-2-butylammonium)2PbBr4[R-(BrBA)2PbBr4and S-(BrBA)2PbBr4], which show low mechanical strength and significant piezoelectric strain coefficients that are advantageous for mechanoelectrical energy conversion. Benefiting from these virtues, the R-(BrBA)2PbBr4@PBAT and S-(BrBA)2PbBr4@PBAT [PBAT = poly(butyleneadipate-co-terephthalate)] composite films show prominent underwater ultrasound detection performance with a transmission effectivity of 12.0% using a 10.0 MHz probe, comparable with that of a polyvinylidene fluoride (PVDF) device fabricated in the same conditions. Density functional theory calculations reveal that R-(BrBA)2PbBr4and S-(BrBA)2PbBr4have a beneficial acoustic impedance (5.07–6.76 MRayl) compatible with that of water (1.5 MRayl), which is responsible for the facile ultrasound-induced electricity generation. These encouraging results open up new possibilities for applying piezoelectric HOIPs in underwater ultrasound detection and imaging technologies.

Byline: Tao. Qin, Pu. Chun, Fei-Fei. Li, Sheng-Bo. Yu, Kun. Hwang, Hong-Jin. Sui Purpose: Ocular suspensory ligament is an important part of the lower eyelid retractors. However, there is a [...]

Carbohydrates have a protein sparing effect, but long-term feeding of a high-carbohydrate diet (HCD) leads to metabolic disorders due to the limited utilization efficiency of carbohydrates in fish. How to mitigate the negative effects induced by HCD is crucial for the rapid development of aquaculture. Uridine is a pyrimidine nucleoside that plays a vital role in regulating lipid and glucose metabolism, but whether uridine can alleviate metabolic syndromes induced by HCD remains unknown. In this study, a total of 480 Nile tilapia (Oreochromis niloticus) (average initial weight 5.02 ± 0.03 g) were fed with 4 diets, including a control diet (CON), HCD, HCD + 500 mg/kg uridine (HCUL) and HCD + 5,000 mg/kg uridine (HCUH), for 8 weeks. The results showed that addition of uridine decreased hepatic lipid, serum glucose, triglyceride and cholesterol (P < 0.05). Further analysis indicated that higher concentration of uridine activated the sirtuin1 (sirt1)/adenosine 5-monophosphate-activated protein kinase (AMPK) signaling pathway to increase lipid catabolism and glycolysis while decreasing lipogenesis (P < 0.05). Besides, uridine increased the activity of glycogen synthesis-related enzymes (P < 0.05). This study suggested that uridine could alleviate HCD-induced metabolic syndrome by activating the sirt1/AMPK signaling pathway and promoting glycogen synthesis. This finding reveals the function of uridine in fish metabolism and facilitates the development of new additives in aquatic feeds.

In higher plants, the shoot apical meristem produces lateral organs in a regular spacing (phyllotaxy) and timing (plastochron). The molecular analysis of mutants associated with phyllotaxy and plastochron would increase our understanding of the mechanism of shoot architecture formation. In this study, we identified mutant mnd8ynp5that shows an increased rate of leaf emergence and a larger number of nodes in combination with a dwarfed growth habit from an EMS-treated population of the elite barley cultivar Yangnongpi 5. Using a map-based cloning strategy, the mnd8gene was narrowed down to a 6.7-kb genomic interval on the long arm of chromosome 5H. Sequence analysis revealed that a C to T single-nucleotide mutation occurred at the first exon (position 953) of HORVU5Hr1G118820, leading to an alanine (Ala) to valine (Val) substitution at the 318th amino acid site. Next, HORVU5Hr1G118820was defined as the candidate gene of MND8encoding 514 amino acids and containing two multidrug and toxic compound extrusion (MATE) domains. It is highly homologous to maize Bige1and has a conserved function in the regulation of plant development by controlling the leaf initiation rate. Examination of modern barely varieties showed that Hap-1 was the dominant haplotype and was selected in barley breeding around the world. Collectively, our results indicated that mnd8ynp5is a novel allele of the HORVU5Hr1G118820gene that is possibly responsible for the shortened plastochron and many noded dwarf phenotype in barley.

Peanut pod shape is a heritable trait which affects the market acceptance of in-shell peanut products. In order to determine the genetic control of pod shape, six component traits of pod shape (pod length, pod width, pod length/width ratio, pod roundness, beak degree and constriction degree) were measured using an image-based phenotyping method. A recombinant inbred line (RIL) population consisting of 181 lines was phenotyped across three environments. Continuous distributions and transgressive segregations were demonstrated in all measured traits and environments. Significant correlations were found among most component traits with broad-sense heritability ranging from 0.87 to 0.95. Quantitative trait locus (QTL) analysis yielded 26 additive QTLs explaining 3.79 to 52.37% phenotypic variations. A novel, stable and major QTL region conditioning multiple shape features was detected on chromosome 2, which spans a 10.81-Mb genomic region with 543 putative genes. Bioinformatics analysis revealed several candidate genes in this region. In addition, 73 pairs of epistatic interactions involving 92 loci were identified for six component traits explaining 0.94–6.45% phenotypic variations. These results provide new genetic loci to facilitate genomics-assisted breeding of peanut pod shape.

Piezoelectric hybrid organic-inorganic perovskites (HOIPs) have emerged as promising materials for the development of self-powered electronic devices. These hybrid systems generally have low elastic moduli and are also intrinsically brittle, limiting their applications in mechanical-to-electrical energy conversion. Here, we report the synthesis of TMCM-CdCl3/PDMS (TMCM, trimethylchloromethyl ammonium; Cl, chloride; PDMS, polydimethylsiloxane) composites with high piezoelectricity. The TMCM-CdCl3micro-rods can adhere with PDMS chains via the C–H···Cl interactions, leading to effective absorption of strain and corresponding efficient conversion to electric polarization. As a result, the energy harvesting devices made by the composite films give a high power density up to 115.2 μW/cm2, catching up with those of the state-of-the-art ceramic counterparts. In addition, the composite devices can harvest human motion energy and sense delicate body gestures. This work demonstrates that the piezoelectric HOIP/polymer composites can serve as promising materials for the development of self-powered flexible and wearable devices.

Introduction: This study was conducted to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative sleep quality of patients undergoing gastrointestinal tumor surgery and to verify the possible mechanism. Methods: Eighty-three patients were allocated to the TEAS or Sham group. Patients in the TEAS group received TEAS treatment (disperse-dense waves; frequency, 2/100 Hz) on bilateral Shenmen (HT7), Neiguan (PC6) and Zusanli (ST36) points for 30 min each time, total three times in the perioperative period. In the Sham group, electrodes were placed; however, no current was given. Sleep quality was assessed on the day before surgery (P1) and the first and third days after surgery (D1 and D3) using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). Postoperative pain was assessed using visual analog scale (VAS) 72 h postoperatively. The incidences of abdominal distension, dizziness, postoperative nausea and vomiting (PONV) and pulmonary complications were recorded. Serum levels of inflammatory cytokines and the expression of key factors of oxidative stress and key molecules of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway were measured. Results: TEAS ameliorated sleep quality at D1 and D3 (PSQI P&lt; 0.05, AIS P&lt; 0.05) and decreased postoperative pain as demonstrated by lower VAS scores compared to the Sham group (P&lt; 0.05). The incidences of abdominal distension and PONV were also lower in the TEAS group. Markers of oxidative stress were increased (P&lt; 0.05), and the serum concentration of interleukin-6 (IL-6) was significantly lower in the TEAS group. The key mediators of the Nrf2/ARE pathway were enhanced after TEAS. Conclusion: Perioperative TEAS improved postoperative sleep quality, reduced postoperative pain and alleviated postoperative adverse effects in patients undergoing laparoscopic gastrointestinal tumor surgery resection. This may be associated with activating Nrf2/ARE signal pathway and decreasing its inflammatory actions. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx), ChiCTR2100054971.

Modern people generally suffer from α-linolenic acid (ALA) deficiency, since most staple food oils are low in ALA content. Thus, the enhancement of ALA in staple oil crops is of importance. In this study, the FAD2and FAD3coding regions from the ALA-king species Perilla frutescenswere fused using a newly designed double linker LP4-2A, driven by a seed-specific promoter PNAP, and engineered into a rapeseed elite cultivar ZS10 with canola quality background. The mean ALA content in the seed oil of PNAP:PfFAD2–PfFAD3(N23) T5 lines was 3.34-fold that of the control (32.08 vs 9.59%), with the best line being up to 37.47%. There are no significant side effects of the engineered constructs on the background traits including oil content. In fatty acid biosynthesis pathways, the expression levels of structural genes as well as regulatory genes were significantly upregulated in N23 lines. On the other hand, the expression levels of genes encoding the positive regulators of flavonoid-proanthocyanidin biosynthesis but negative regulators of oil accumulation were significantly downregulated. Surprisingly, the ALA level in PfFAD2–PfFAD3transgenic rapeseed lines driven by the constitutive promoter PD35Swas not increased or even showed a slight decrease due to the lower level of foreign gene expression and downregulation of the endogenous orthologous genes BnFAD2and BnFAD3.

Hybrid organic-inorganic piezoelectrics have received considerable attention in recent years owing to their fascinating performance, facile synthesis, and mechanical flexibility. However, the reported systems usually contain toxic heavy metals or are unstable due to sensitive metal halide bonds in air. In this context, eco-friendly and stable hybrid materials with excellent piezoelectric properties are highly sought after. Here, a new stable zero-dimensional hybrid piezoelectric, [Me-V]3Mn(SCN)5(Me-V, 1-methyl-[4,4′]-bi-pyridinium), based on a pseudo-halogen environmentally friendly anion of SCN−was synthesized. More importantly, the mechanical energy harvesting properties of its flexible composite films, [Me-V]3Mn(SCN)5/PBAT (PBAT, polybutylene adipate terephthalate), with a series of weight ratios (1, 5, 10, 15, and 20 wt%) of [Me-V]3Mn(SCN)5are reported. Experimental results demonstrate that the 15 wt% [Me-V]3Mn-(SCN)5/PBAT devices present an exceptional performance in energy harvesting, which can produce a maximum output voltage of 18.49 V and a power density of 7.88 µW cm−2under an applied force of only 0.03 MPa, catching up with those of the state-of-the-art piezoelectric energy harvesting devices. Meanwhile, a typical device was demonstrated to exhibit excellent mechanical durability under 5500 cycles and environmentally stable over 60 days. Furthermore, the devices also show good sensitivity in monitoring human body motions, including finger tapping, wrist and elbow bending, and foot stepping. This work proves that lead- and halide-free hybrid piezoelectrics can serve as eco-friendly materials for flexible sensing and energy harvesting.

Chemotherapy, targeted therapy, and immunotherapy are effective against most tumors, but drug resistance remains a barrier to successful treatment. Lysine-specific demethylase 1 (LSD1), a member of histone demethylation modifications, can regulate invasion, metastasis, apoptosis, and immune escape of tumor cells, which are associated with tumorigenesis and tumor progression. Recent studies suggest that LSD1 ablation regulates resensitivity of tumor cells to anticarcinogens containing immune checkpoint inhibitors (ICIs) via multiple upstream and downstream pathways. In this review, we describe the recent findings about LSD1 biology and its role in the development and progression of cancer drug resistance. Further, we summarize LSD1 inhibitors that have a reversal or resensitive effect on drug resistance and discuss the possibility of targeting LSD1 in combination with other agents to surmount resistance.

Cobalt-based catalysts are ideal for CO2reduction reaction (CO2RR) due to the strong binding and efficient activation of CO2molecules on cobalt. However, cobalt-based catalysts also show low free energy of hydrogen evolution reaction (HER), making HER competitive with CO2RR. Therefore, how to improve the product selectivity of CO2RR while maintaining the catalytic efficiency is a great challenge. Here, this work demonstrates the critical roles of the rare earth (RE) compounds (Er2O3and ErF3) in regulating the activity and selectivity of CO2RR on cobalt. It is found that the RE compounds not only promote charge transfer but also mediate the reaction paths of CO2RR and HER. Density functional theory calculations verify that the RE compounds lower the energy barrier of *CO → CO conversion. On the other hand, the RE compounds increase the free energy of HER, which leads to the suppression of HER. As a result, the RE compounds (Er2O3and ErF3) improve the CO selectivity of cobalt from 48.8 to 69.6%, as well as significantly increase the turnover number by a factor of over 10.

Low expression levels of E2F3a and caspase 8-associated protein 2 (CASP8AP2) are associated with poor outcomes in children with acute lymphoblastic leukemia. Our previous study showed that a combined assessment of E2F3a and CASP8AP2 expression was more accurate in predicting relapse in children with acute lymphoblastic leukemia. However, the underlying mechanism remains unclear. In this study, the interaction between E2F3a and CASP8AP2 and its role in the regulation of histone expression, cell proliferation, the cell cycle, and chemosensitivity were investigated. Exogenous E2F3a-GST was coprecipitated with CASP8AP2-FLAG in HEK-293T cells. E2F3a was colocalized with CASP8AP2-GFP in the nucleus. The replication-dependent histones H2A and H2B were significantly upregulated when E2F3a or CASP8AP2 was overexpressed in HEK-293T or 697 cells and downregulated by E2F3a or CASP8AP2 knockdown. E2F3a and CASP8AP2 could collaboratively enhance the transcriptional activity of HIST1H2AGand HIST1H2BK. Both CASP8AP2 and E2F3a are involved in S phase progression. E2F3a and CASP8AP2 also affected the sensitivity of leukemic cells to daunorubicin. Therefore, CASP8AP2 and E2F3a collaboratively regulated replication-dependent histone expression, cell cycle progression, and chemosensitivity of leukemic cells.

ABSTRACTDuring the COVID-19 pandemic, the Internet has become one of the most crucial platform for people all over the world. The online market and online shopping have become the most popular pastimes among internet users. This study gathered 560 valid responses from Thai and Taiwanese participants. The results from experiment revealed that the social cues and expertise of reviewers had a substantial impact on the responses of Thailand and Taiwan customers. The results of this study indicated the level of social cues has a significant main effect on trust, purchase intention, and perceived information quality on the customer’s response. Furthermore, the expertise of reviewers resulted in a significantly higher level of trust, purchase intention, and perceived information quality for the customer. Our study results suggest that the level of social cues and the expertise of reviewers in the online store website have an influence on consumer perception in both countries.

Mechanical performance prediction is the key to the transformation and upgrading of steel enterprises to intelligent manufacturing. Due to time-varying manufacturing data, the traditional prediction model of mechanical properties of hot-rolled strip may cause performance degradation or even failure in its use. An MDA-JITL model was thus proposed to handle the modeling problem of complex time-varying data. Relevant parameters were first chosen and normalized. Then, a distance measurement method combining the importance of data attributes and time characteristics was designed to select the most suitable samples for on-line local modeling. After that, using the chosen dataset, a linear local model was created to predict target sample. Finally, an uncertainty evaluation method was designed to evaluate the uncertainty of prediction results. Furthermore, the appropriate dataset partition and off-line simulation experiment scheme were created based on the peculiarities of hot-rolling production. The suggested model performs much better than the classic global model when applied to actual production data from a steel plant. The stability of its prediction accuracy is demonstrated in a simulation prediction for up to five months. Moreover, there is a high link between the uncertainty evaluation metrics and the prediction error of the model, reducing the field sampling rate by 30% in industrial applications in the latest year.

Herein, we report an unprecedented asymmetric guanidinium polyiodate, namely, C(NH2)3(I3O8)(HI3O8)(H2I2O6)(HIO3)4·3H2O (1). The title compound was obtained via the hybridization of polyiodate anions and planar π-conjugated C(NH2)3+; meanwhile, its strong second-harmonic-generation (SHG) response (2.1 × KDP, where KDP = KH2PO4) and wide band gap (3.89 eV) were mainly dominated by the synergy effect of the aforementioned structural units.

Cyanide is well known as a highly toxic substance and is widely present in nature. Plant ash is also rich in cyanide, but its function in plants is rarely reported. This study used C3 and C4 plants to investigate the effects of burned plant ash and its cyanide extract on tomato seed germination. The results showed that the germination of tomato seeds was affected by different plant ash with great differences, among which soybean (C3 strain) and corn (C4 strain) straw ash had the best-promoting effect. In addition, all cyanide extracts from C3 and C4 straws were shown to promote tomato seed germination at lower concentrations, whereas the opposite effects were observed at higher concentrations. Notably, the content of cyanide in C4 plant ash was generally higher than that of C3 plants. The findings in this study provide new insights into further analysis of the function of cyanide in C3 and C4 plants in the future.

Introduction: Bloodstream infection (BSI) is a significant factor contributing to hospitalization and high mortality rates among human immunodeficiency virus(HIV)-positive patients. Therefore, the timely detection of this condition is of utmost importance. Blood culture is considered the gold standard for diagnosing BSIs. Currently, BD BACTEC™ Plus Aerobic/F culture bottles and the BD BACTEC™ Myco/F Lytic culture bottles can be used for blood culture. This study aimed to evaluate the efficacy of two different types of culture bottles in diagnosing BSIs in patients with HIV. Methods: A retrospective analysis was conducted on HIV-positive patients hospitalized in the Infection Department of Wenzhou Central Hospital between July 2019 and October 2021. A total of 246 pairs of blood samples were included, consisting of an aerobic culture vial and a Myco/F culture vial. Blood culture results and clinical diagnosis were utilized to identify the presence of BSI. Results: Out of 246 cases, 84 cases had positive blood cultures. Fungal BSIs, particularly Talaromyces marneffeiBSIs, were the most prevalent among patients with HIV. The positive rate of Myco/F culture bottles (89.29%) was significantly higher compared with aerobic culture bottles (69.05%; P= 0.001). In the diagnosis of fungal BSIs, the positive rate of Myco/F culture bottles was 88.57%, which was significantly higher than that of aerobic culture bottles (72.86%; P= 0.018). The Myco/F culture bottle has more advantages in diagnosing Talaromyces marneffeiBSIs (P=0.028). In addition, mycobacteria were exclusively detected in Myco/F culture bottles. Conclusions: Fungal BSIs are the predominant type of infections in HIV-positive patients. Myco/F culture bottles exhibit noteworthy attributes of high positive rate in diagnosing HIV combined with BSI. These advantages are conducive to obtaining accurate culture results and minimizing missed diagnoses.

Background: Durable remission has been observed in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with chimeric antigen receptor (CAR) T-cell therapy. Consequently, hazard functions for overall survival (OS) are often complex, requiring the use of flexible methods for extrapolations. Objectives: We aimed to retrospectively compare the predictive accuracy of different survival extrapolation methods and evaluate the validity of goodness-of-fit (GOF) criteria-based model selection for CAR T-cell therapies in R/R LBCL. Methods: OS data were sourced from JULIET, ZUMA-1, and TRANSCEND NHL 001. Standard parametric, mixture cure, cubic spline, and mixture models were fit to multiple database locks (DBLs), with varying follow-up durations. GOF was assessed using the Akaike information criterion and Bayesian information criterion. Predictive accuracy was calculated as the mean absolute error (MAE) relative to OS observed in the most mature DBL. Results: For all studies, mixture cure and cubic spline models provided the best predictive accuracy for the least mature DBL (MAE 0.013‒0.085 and 0.014‒0.128, respectively). The predictive accuracy of the standard parametric and mixture models showed larger variation (MAE 0.024‒0.162 and 0.013‒0.176, respectively). With increasing data maturity, the predictive accuracy of standard parametric models remained poor. Correlation between GOF criteria and predictive accuracy was low, particularly for the least mature DBL. Conclusions: Our analyses demonstrated that mixture cure and cubic spline models provide the most accurate survival extrapolations of CAR T-cell therapies in LBCL. Furthermore, GOF should not be the only criteria used when selecting the optimal survival model.

ABSTRACT In this study, the corrosion inhibition performance of steel reinforcement in the simulated concrete pore solution containing 3.5 wt.% NaCl in the presence of a tailored cationic type of [...]

The article discusses the goals of various world leaders in the fields of health, technology, and the environment, and it provides quotes from individuals such as Canadian Prime Minister Justin Trudeau and philanthropist Melinda Gates. Stanford University Human-Centered AI Institute co-director Fei-Fei Li's attitude about diversity in the artificial intelligence research field is assessed, along with issues involving antibiotics development, digital currency safety, and child-mortality rates.